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Catalytic enantioselective synthesis of quaternary carbon stereocentres

Nature volume 516, pages 181–191 (2014)Cite this article

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Abstract

Quaternary carbon stereocentres—carbon atoms to which four distinct carbon substituents are attached—are common features of molecules found in nature. However, before recent advances in chemical catalysis, there were few methods of constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules. This progress now makes it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials.

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Figure 1: Quaternary stereocentres are important structural features of many biologically active molecules, as exemplified by the natural products cortisone and morphine.
Figure 2: The use of catalytic enantioselective Diels–Alder reactions to synthesize natural products containing quaternary stereocentres.
Figure 3: Examples of other catalytic enantioselective cycloaddition reactions used to prepare products containing quaternary stereocentres.
Figure 4: Catalytic enantioselective polyene cyclizations to construct polycyclic products having quaternary stereocentres.
Figure 5: Transition metal-catalysed insertion reactions that form quaternary stereocentres.
Figure 6: Enantioselective copper-catalysed conjugate additions to construct quaternary stereocentres.
Figure 7: Use of the enantioselective intramolecular Stetter reaction and allylic alkylation reactions to construct quaternary stereocentres.
Figure 8: Use of palladium-catalysed asymmetric allylic alkylation reactions for constructing quaternary centres in alkaloid and terpenoid natural products.
Figure 9: Miscellaneous methods involving the union of a catalytically generated chiral carbon electrophile with a carbon nucleophile.
Figure 10: Enantioselective desymmetrization reactions of precursors containing prochiral quaternary carbons.

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Acknowledgements

Our research in this area was supported by the US National Institutes of Health (R01 GM030859 and GM098601).

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Authors and Affiliations

  1. Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, 92697-2025, California, USA

    Kyle W. Quasdorf & Larry E. Overman

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  1. Kyle W. Quasdorf
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Both K.W.Q. and L.E.O. prepared the manuscript.

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Correspondence to Larry E. Overman.

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The authors declare no competing financial interests.

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Quasdorf, K., Overman, L. Catalytic enantioselective synthesis of quaternary carbon stereocentres. Nature 516, 181–191 (2014). https://doi.org/10.1038/nature14007

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